1. Field of the Invention
This invention relates to an incubator for a biochemical analysis apparatus in which a sample liquid such as blood or urine is spotted on a reagent layer (spreading layer) of a dry frameless chemical analysis film and the concentration of a predetermined biochemical substance in the sample liquid is determined through a change in the optical density of the reagent layer due to a chemical reaction, a biochemical reaction, an immunoreaction or the like of the reagent in the reagent layer with the predetermined biochemical substance, the incubator being for incubating the frameless chemical analysis film spotted with the sample liquid at a constant temperature to promote the reaction.
2. Description of the Prior Art
There has been put into practice a chemical analysis slide having a "dry-to-touch" chemical analysis film with which the content of a specific chemical component contained in a sample liquid, the activity thereof or the content of a solid component can be quantitatively analyzed by only spotting a droplet of the sample liquid on the film. When quantitatively analyzing the chemical components or the like contained in a sample liquid using such a chemical analysis slide, a droplet of the sample liquid is spotted on the film (on the spreading layer when the film is provided with a spreading layer and directly on the reagent layer when the film is not provided with a spreading layer) and is held at a constant temperature for a predetermined time (incubation) in an incubator so that coloring reaction occurs, and the optical density of the color formed by the coloring reaction is optically measured. That is, measuring light containing a wavelength which is preselected according to the combination of the component to be analyzed and the reagent contained in the reagent layer of the film is projected onto the film and the optical density of the film is measured. Then the concentration or the activity of the component to be analyzed is determined on the basis of the optical density using a calibration curve which represents the relation between the concentration of the predetermined biochemical substance and the optical density.
The chemical analysis slide generally comprises a dry chemical analysis film chip and a frame of organic polymer which holds flat the chemical analysis film chip which is apt to curl or warp in a dry state. The chemical analysis film chip is generally composed of a support sheet of organic polymer or the like and at least one reagent layer (containing therein a reagent) formed on the support sheet. Preferably a spreading layer is formed on the reagent layer.
However the chemical analysis slide is disadvantageous in that each of the parts of the incubator for incubating the chemical analysis slides must be larger in size by the amount corresponding to the size of the frame, which obstructs reduction in size of the biochemical analysis apparatus and at the same time results in reduction of the number of the chemical analysis films which can be accommodated in an incubator of a given size. When the number of the chemical analysis films which can be accommodated in an incubator is small, the overall throughput capacity of the biochemical analysis apparatus cannot be increased.
In view of the observation, we have proposed to use a chemical analysis film chip without the frame (will be referred to as a "frameless chemical analysis film", hereinbelow). However since the frameless chemical analysis film is apt to curl in a dry state as described above and the state of curl changes when the sample liquid is spotted thereon, the frameless chemical analysis film should be held flat in the incubator. Further the frameless chemical analysis film should be held tightly enclosed in the incubator.
In the incubator, the frameless chemical analysis film spotted with the sample liquid is heated to a predetermined temperature and held at the temperature. For instance, in U.S. Pat. Nos. 4,219,529 and 4,298,571, there is disclosed an incubator for the chemical analysis slides in which a chamber is provided to cover a plurality of cells each for accommodating one chemical analysis slide and the atmosphere in the chamber is heated to and held at a predetermined temperature.
In the chamber, each chemical analysis slide must be held in place in order to keep constant the distance from the light measuring optical system, to facilitate inserting and taking out the slide into and from the incubator, and to transmit heat to the slide. In the United States patents identified above, each slide is held in place by a spring-like pressing member. Since the spring-like pressing member is not ready to transmit heat due to its shape, the temperature in the chamber is controlled and the pressing member (including a cover which is brought into contact with the slide by the pressing member) are heated by way of air. In order to keep constant the temperature in the chamber, the chamber is kept closed.
Since the pressing member is heated through air in such an incubator having a temperature-controlled chamber, the temperature of the pressing member is lowered when a cold slide is inserted into the chamber and it takes a long time for the pressing member to recover the predetermined incubating temperature. (Generally the slides are stored at a low temperature to prevent deterioration of the measuring performance and accordingly the temperature of the slide before insertion into the chamber is low.) In order to suppress such a problem, it is necessary to pre-heat the slide before insertion into the chamber so that the fluctuation in temperature of the pressing member is suppressed. Further upon starting up the biochemical analysis apparatus, it takes a long starting-up time to heat the atmosphere in the incubator to the predetermined incubating temperature due to the air heating structure of the chamber.
Further in the air heating structure of the chamber, the chamber must be tightly enclosed in order to keep constant the temperature in the chamber, which requires a shutter for opening and closing the slide port and complicates the structure of the incubator. Further since the cells for accommodating the slides are enclosed in the chamber, interfering gas which can be generated during coloring reaction in one of the cells and can affect the coloring reaction in another cell is confined in the chamber, which can result in deterioration in accuracy of measurement. Further, the members for sealing the chamber, the mechanism of shutter and the like adds to the manufacturing cost of the incubator. Thus it is preferred that the slide be heated tightly enclosed in each cell so that the coloring reaction in each cell cannot be affected by evaporation of the sample liquid or interfering gases confined in the chamber.
There has also been known a technique in which a plurality of cells each for accommodating a slide are formed in a base plate of metal and a pressing member is provided to tightly enclose, from above, the slide accommodated in each cell, the base plate being heated by heater and the pressing member being heated by way of an upper member which supports the pressing member and is heated by a heater wound therearound. In this technique, the chamber is not necessary.
When dry frameless chemical analysis films are incubated in such an incubator in which no chamber is formed and the frameless chemical analysis films are directly heated, the shutter for opening and closing the slide port can be eliminated, preheating of the slide becomes unnecessary, the starting-up time can be shortened, and the problem of influence of interfering gases can be avoided. However since the part of the upper side of the frameless chemical analysis film on which the sample liquid is applied cannot be directly touched, the part of the frameless chemical analysis film cannot be sufficiently heated to the incubating temperature.
That is, when a frameless chemical analysis film in a curled state is flattened by a flat pressing member, the lower side of the pressing member is brought into contact with the sample liquid on the film and the sample liquid adheres to the pressing member and can contaminate the sample liquid on the frameless chemical analysis film to be incubated next when the pressing member flattens the next film.
Thus, in the case of the frameless chemical analysis film, it is preferred that the film be heated only by conduction of heat from the lower side thereof without contact heating of the upper side of the film. In this case, the frameless chemical analysis film can be held flat, for instance, by pressing down a part of the margin of the film which is free of the sample liquid. However since the incubator cell must tightly enclose the film to prevent evaporation of the sample liquid and must be able to surely hold the film irrespective of fluctuation in the state of curl and/or thickness of the film, the incubator cell becomes complicated in structure. Further in order to reduce the amount of interfering gas and/or the sample liquid adhering to the incubator cell, it is preferred that the incubator cell be molded from a limited plastic material.
When the incubator cell is formed from plastic material, a problem of moisture condensation is involved due to low heat conductivity of the plastic material. That is, since the frameless chemical analysis film in the incubator cell is heated by heat from the lower side and the heat of the film is hard to be transmitted to the incubator cell due to a small contact area between the film and the incubator cell, the film can be surely heated to a predetermined temperature. On the other hand, since the temperature of the inner surface of the incubator cell is kept low and the enclosed space in the incubator cell is held at 100% humidity, moisture is condensed on the inner surface of the incubator cell, which adversely affects the measurement and involves problems due to absorption of interfering gases.